crossing96/oncoscreening huggingface dataset:
Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.	BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).	bladder
Survival and Characteristics of Bladder Cancer: Analysis of the Malaysian National Cancer Registry.	BACKGROUND: Bladder cancer ranked ninth of principal male cancer in Malaysia. This study aimed to evaluate the clinical characteristics and survival of bladder cancer patients in Malaysia. METHODS: A retrospective cohort study was conducted by obtaining records in the Malaysian National Cancer Registry. Patients aged 15 years old and above with diagnosis date between 2007 and 2011 were included. Death was updated until 31 December 2016. Five-year observed survival and median survival time were determined by the life table method and Kaplan-Meier estimate method. RESULTS: Among 1828 cases, the mean (SD) age of diagnosis was 64.9 (12.5) years. The patients were predominantly men (78.7%), Malay ethnicity (49.4%) and transitional cell carcinoma (78.2%). Only 14.8% of patients were at stage I. The overall five-year observed survival and median survival time was 36.9% (95% CI: 34.6, 39.1) and 27.3 months (95% CI: 23.6, 31.0). The highest five-year observed survival recorded at stage I (67.6%, 95% CI: 62.0, 73.3) and markedly worsen at stage II (34.3%, 95% CI: 27.9, 40.8), III (25.7%, 95% CI: 18.7, 32.6) and IV (12.2%, 95% CI: 8.1, 16.3). CONCLUSIONS: Survival of bladder cancer patients in Malaysia was lower with advancing stage. The cancer control programme should be enhanced to improve survival.	bladder
Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy.	There have been critical problems in the non-surgical treatment for bladder cancer, especially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone-mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non-surgical therapy for bladder cancer. This may indicate the possibility of anti-androgenic and anti-estrogenic drugs, apart from their direct anti-tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor-α, and estrogen receptor-β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.	bladder
Controlling Nutritional Status Score Evaluates Prognosis in Patients With Non-Muscle Invasive Bladder Cancer.	OBJECTIVE: We investigated the clinical value of the Controlling Nutritional Status score in evaluating the prognosis of patients with non-muscle invasive bladder cancer. METHODS: We conducted a retrospective analysis of the clinical data of 88 patients with non-muscle invasive bladder cancer who underwent transurethral resection of bladder tumor or partial cystectomy between January 2011 and May 2015 in a single center. The patients were divided into groups base on high (>1) and low (≤1) Controlling Nutritional Status score. RESULTS: Clinical and demographic data of the patient groups were analyzed using the Kaplan-Meier method and log-rank test to generate survival curves. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Among the participants, the male-to-female ratio was 70:18 and median age was 64.5 years (range, 25-84 years). The numbers of patients with Controlling Nutritional Status score of 0, 1, 2, 3, 4, 5, and 6 were 26 (29.55%), 21 (23.86%), 20 (22.73%), 12 (13.64%), 5 (5.68%), 1 (1.14%), and 3 (3.41%), respectively. The 5-year recurrence rate was 29 out of 88 patients (32.95%). The recurrence-free survival of the high-score group was significantly lower than that of the low-score group (P < 0.001). On univariate analysis, age, smoking history, Controlling Nutritional Status score, depth of tumor invasion, pathological grade, and tumor diameter were related to the prognosis of patients with non-muscle invasive bladder cancer. On multivariate analysis, the Controlling Nutritional Status score (hazard ratio, 4.938; 95% confidence interval, 1.392-17.525; P = 0.013) was an independent factor affecting the recurrence-free survival of patients with non-muscle-invasive bladder cancer. CONCLUSION: Therefore, the Controlling Nutritional Status score could be a simple, cost-effective, and reliable predictor of prognoses among of patients with non-muscle-invasive bladder cancer.	bladder
Is There a Detrimental Effect of Antibiotic Therapy in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Pembrolizumab?	In locally advanced and metastatic malignancies, antibiotic (ATB) therapy has a negative effect on immunotherapy efficacy. Therefore, we aimed to evaluate whether ATB therapy and use of specific ATB classes with concomitant neoadjuvant pembrolizumab affected pathologic complete response (ypT0N0) and relapse-free survival (RFS) for patients with clinical T2-4N0M0 bladder cancer enrolled in the PURE-01 study. Of the 149 patients evaluated, 48 (32%) received any concomitant ATB therapy. The ATB class most commonly administered was fluoroquinolones (16 patients; 33%). In the ATB cohort, seven patients (15%) achieved ypT0N0 status, compared to 50 (50%; p < 0.001) in the untreated group. Moreover, ATB use was negatively associated with ypT0N0 status (odds ratio 0.18, 95% confidence interval [CI] 0.05-0.48; p = 0.001). The 24-mo RFS rate was 63% (95% CI 48-83%) in the ATB group versus 90% (95% CI 83-97) in the untreated group. We found that ATB use was associated with a higher recurrence rate (hazard ratio [HR] 2.64, 95% CI 1.08-6.50; p = 0.03). Exploratory analyses showed that fluoroquinolone use was associated with a higher recurrence rate (HR 3.28, 95% CI 1.12-9.60; p = 0.03). Our study revealed an association between ATB use and neoadjuvant immunotherapy efficacy in an intention-to-cure population, highlighting the need for future studies to better investigate this relationship. PATIENT SUMMARY: The efficacy of immunotherapy for cancer is influenced by several patient and tumor factors, including the use of antibiotics. We found that antibiotics taken at the same time as immunotherapy drugs were associated with lower rates of complete response and of recurrence-free survival among patients with muscle-invasive bladder cancer. These findings need to be confirmed in future studies.	bladder
Comparison of Genomic Characterization in Upper Tract Urothelial Carcinoma and Urothelial Carcinoma of the Bladder.	BACKGROUND: Different genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity. MATERIALS AND METHODS: We prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal. RESULTS: There were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB. CONCLUSION: UTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB. IMPLICATIONS FOR PRACTICE: This study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.	bladder
Propofol suppressed cell proliferation and enhanced apoptosis of bladder cancer cells by regulating the miR-340/CDK2 signal axis.	BACKGROUND: As widely reported, propofol can effectively inhibit tumors development. However, little is known about the molecular mechanisms. Here, we proved that propofol regulated miR-340/CDK2 axis to suppress bladder cancer progression in vitro. METHODS: MicroRNA (MiR)-340 expression in 5637 cells was examined using qRT-PCR. Cyclin-dependent kinase2 (CDK2) expression was detected using both qRT-PCR and western blot. The levels of apoptosis-related proteins and cell cycle-related proteins were evaluated using western blot. CCK-8 assay and BrdU assay were conducted to evaluate cell proliferation. Moreover, flow cytometry assay was employed to assess cell cycle and cell apoptosis. Finally, dual luciferase reporter assay was employed to verify the binding relationship between miR-340 and CDK2. RESULTS: Here we showed that propofol treatment inhibited cell proliferation of 5637 cells but enhanced cell apoptosis. Propofol upregulated miR-340 in a dose and time dependent manner. MiR-340 inhibitor could reverse the effect of propofol on the proliferation and apoptosis of 5637 cells. Next, dual luciferase reporter assay displayed that miR-340 directly bound to the 3'-UTR of CDK2. Finally, inhibition of CDK2 could partly reversed the effect of miR-340 inhibitor on cell proliferation and cell apoptosis of propofol-treated 5637 cells. CONCLUSION: In total, our results proved that targeting miR340/CDK2 axis was novel to enhance the anti-tumor effects of propofol in bladder cancer in vitro, and our study provided alternative therapeutic strategies for clinical treatment of bladder cancer.	bladder
Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes.	BACKGROUND: Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood. METHODS: In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR. RESULTS: Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV. CONCLUSIONS: This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.	bladder
Are there monogenic hereditary forms of bladder cancer or only genetic susceptibilities?	Bladder cancer (BC) is the most common cancer involving the urinary system and the ninth most common cancer worldwide. Tobacco smoking is the most important environmental risk factor of BC. Several single nucleotide polymorphisms have been validated by genome-wide association studies as genetic risk factors for BC. However, the identification of DNA mismatch-repair genes, including MSH2 in Lynch syndrome and MUTYH in MUTYH-associated polyposis, raises the possibility of monogenic hereditary forms of BC. Moreover, other genetic mutations may play a key role in familial and hereditary transmissions of BC. Therefore, the aim of this review is to focus on the major hereditary syndromes involved in the development of BC and to report BC genetic susceptibilities established with genome-wide significance level.	bladder
Guggulsterone induces apoptosis and inhibits lysosomal-dependent migration in human bladder cancer cells.	BACKGROUND: The survival rate and therapeutic options for patients with bladder cancer have improved little in recent decades. Guggulsterone (GS), a phytoestrogen, has been investigated as an anticancer drug in various malignancies. PURPOSE: The present study aimed to evaluate the anticancer effects of E-isomer and Z-isomer GS in the human bladder cancer cell lines TSGH8301 (low-grade) and T24 (high-grade) and their underlying mechanisms. METHODS: The cell survival effect of GS was investigated by the MTT and colony formation assays in bladder cancer cell lines. Flow cytometry was used to analyze the cell cycle and cell death. Migration ability was measured by wound healing and transwell assays. Protein expression was determined by Western blot after GS treatment. The potency of GS on subcutaneous TSGH8301 bladder tumors was evaluated using an in vivo imaging system. RESULTS: E-isomer GS reduced the survival rate of both low- and high-grade human bladder cancer cells. GS caused cell cycle arrest, accompanied by the decrease and increase in cyclin A and p21 levels, respectively. Additionally, caspase-dependent apoptosis was observed following GS treatment. Furthermore, GS treatment downregulated mTOR-Akt signaling and induced autophagy with p62 and LC3β-II expression. Moreover, the farnesoid X receptor was involved in GS-inhibited cell growth. In addition, GS reduced the migration ability with a decrease in integrin-focal adhesion kinase and myosin light chain. Interestingly, the suppression of GS-mediated migration was prevented by the lysosomal inhibitor ammonium chloride (NH(4)Cl). GS also reduced TSGH8301 bladder cancer cell progression by increasing the level of p21, cleaved caspase 3, cleaved poly (ADP-ribose) polymerase (PARP), and LC3β-II in vivo. CONCLUSIONS: The current findings suggest that GS treatment may serve as a potential anticancer therapy for different grades of urothelial carcinoma.	bladder
The diagnostic challenge of suspicious or positive malignant urine cytology findings when cystoscopy findings are normal: an outpatient blue-light flexible cystoscopy may solve the problem.	PURPOSE: To investigate whether outpatient blue-light flexible cystoscopy could solve the diagnostic challenge of positive or suspicious urine cytology findings despite normal white-light flexible cystoscopy results and normal findings on computerized tomography urography, in patients investigated for urothelial cancer. MATERIAL AND METHODS: In a multicentre study, a total of 70 examinations were performed with the use of blue-light flexible cystoscopy (photodynamic diagnosis) after intravesical instillation of the fluorescence agent hexaminolevulinate. The examination started with a conventional white-light flexible cystoscopy and then the settings were switched to use blue light. Suspicious lesions were biopsied. Afterwards, the patients were interviewed regarding their experience of the examinations. RESULTS: Bladder cancer was diagnosed in 29 out of 70 (41%) cases, among them 14/29 (48%) had malignant lesions seen only in blue light. The majority had carcinoma in situ (21/29). Normal findings were seen in 41 cases that underwent BLFC. During the further course, malignancy of the bladder was detected in six cases (9%) and malignancy of the upper urinary tract was detected in one case (1%). The majority of patients (93%) preferred the blue-light flexible cystoscopy performed at the outpatient clinic instead of the transurethral resection under general anaesthesia. CONCLUSION: Blue-light flexible cystoscopy at the outpatient clinic may be a useful tool to solve unclear cases of a malignant or suspicious urinary cytology suggestive of bladder cancer. The procedure was well tolerated by the patients.	bladder
The association between hepatitis C virus infection and renal cell cancer, prostate cancer, and bladder cancer: a systematic review and meta-analysis.	To update the current evidence on whether hepatitis C virus (HCV) infection represents a possible risk factor for renal cell cancer (RCC), prostate cancer (PCa), and bladder cancer (BC). We searched the literature on Pubmed, Web of Science, and Embases before April 2021. A systematic review and meta-analysis were performed. Finally, we extracted 12 studies based on the eligible criteria. Across 11 studies for HCV and RCC, the incorporated RR was 1.28 (95% CI 1.05-1.55), which meant that participants with HCV infection were associated with higher RCC risk. The pooled RR in hazard ratio (HR) subgroup (HR 1.59, 95% CI 1.22-2.08), cohort studies subgroup (RR 1.47, 95% CI 1.18-1.82), and North America subgroup (RR 1.71, 95% CI 1.40-2.09) detected a stronger association between HCV and RCC risk. Although an inverse association was seen for PCa (RR 0.75, 95% CI 0.54-1.03) across seven studies, it was not statistically significant (P = 0.075). There was no significant association between HCV and BC with an incorporated RR of 0.92 (95% CI, 0.82-1.03) across five studies. Our study demonstrated that HCV infection was significantly associated with increased RCC risk. There appeared to be an inverse association for HCV in PCa risk but not statistically significant. No significant association was found between HCV and BC risk. Prospective, large-scale, and well-designed cohort studies are required to validate the association between HCV and RCC, and to investigate the role of HCV on PCa.	bladder
Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment.	BACKGROUND: Polyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of homogeneous polyporus polysaccharide (HPP) activated macrophages in the treatment of bladder cancer. METHODS: 100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Then macrophages derived from THP-1 were treated with different concentrations of HPP (1, 10 and 100 μg/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with HPP. The conditioned medium from HPP-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein. RESULTS: HPP promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. Results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial-mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. CONCLUSION: The findings indicated that HPP inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.	bladder